Many biologically active molecules exist as enantiomers. Although structurally identical, enantiomers can have different effects in biological systems: one isomer may have specific therapeutic activity while the other isomer may have no therapeutic activity or may have entirely different forms of biological activity.
The form in which adrenergic beta-2 agonist drugs presently are used therapeutically in mammals are as racemic mixtures of two isomers (e.g., R- and S-albuterol; R- and S-salmeterol; R- and S-terbutaline). An R-isomer of a racemic compound is structurally identical to the S-isomer and the isomers differ only in that one isomer is a mirror image of the other. Molecules with two chiral centers have four isomers, e.g., RR-formoterol, SS-formoterol, RS-formoterol and SR-formoterol. The therapeutically active isomers (the eutomers) of beta-2 agonists are the R- or RR-isomers, while the S-or SS-isomers usually do not carry therapeutic activity (distomers). An exception is salmeterol, where both isomers carry adrenergic beta-2 agonistic activity and thus either of the isomers of salmeterol can be regarded as a eutomer.
A therapeutic action of beta-2 agonist drugs is to active adrenergic beta-2 receptors and thereby initiate cellular responses, the most well-known in the relaxation of bronchial smooth muscles. Adrenergic beta agonist drugs also have metabolic effects and increase growth, and such effects may reside in either of the isomers. It has now been shown that the beta-agonist eutomer causes improved muscle growth, while a decrease in carcass fat has been established.
The pharmacological effects and the toxicity of adrenergic beta-agonists varies, depending on the animal species and which drug is studied. The therapeutically inactive S-isomer of albuterol has now been found to be approximately equitoxic to the R-isomer. The S-isomers of albuterol and salmeterol have now been found to be metabolized significantly slower than the R-isomers, causing a prolonged presence of residual S-albuterol and S-salmeterol, respectively, to exist in the body.
The most commonly used therapeutic indication for beta-agonists in man is to treat bronchial spasms in asthmatic individuals. Adrenergic beta-agonist drugs also have been shown to inhibit premature contractions (tocolysis) of the pregnant uterus in humans. The potentially hazardous side effects of albuterol in humans include but are not limited to bronchial hyperreactivity, increased intraocular pressure, uterine hyperreactivity (stimulation of uterine contractions) and teratogenic effects of the drug to the fetus.